Reaction #1256736

Reaction equation

acyclovir

Boc-Val

dicyclohexyl carbodiimide

DCC Boc-Val

→

Val-ACV

Solvents

dimethylformamide

Conditions

Workup

1. 1
   workup.STIRRINGstirred for 18 hrs
2. 2
   Filtrationfiltered
3. 3
   OtherThe solvent of the filtrate was partially removed in vacuo
4. 4
   workup.ADDITIONthe impure solution was added dropwise to cold diethyl ether
5. 5
   FiltrationThe resulting precipitate (2) was filtered
6. 6
   Otherdried
7. 7
   Otherfollowed by acidolytic removal (treating Boc-Val-ACV with trifluoroacetic acid (TFA) for 30 min at 0° C.) of the Boc protecting group

Procedure

A mixture of Boc-Val and dicyclohexyl carbodiimide (DCC) in dimethylformamide (DMF) in a ratio of 1:2 DCC/Boc-Val was stirred for 1 hr at 0° C. under nitrogen atmosphere. A solution of acyclovir (1) and 4-N,N(dimethylamino)pyridine (DMAP) was added to the reaction mixture, stirred for 18 hrs and then filtered. The solvent of the filtrate was partially removed in vacuo and the impure solution was added dropwise to cold diethyl ether. The resulting precipitate (2) was filtered and dried, followed by acidolytic removal (treating Boc-Val-ACV with trifluoroacetic acid (TFA) for 30 min at 0° C.) of the Boc protecting group to yield Val-ACV (3). Compound (3) was neutralized by triethylamine (TEA) and treated with the amino acid anhydride of Boc-Val for about 5 hrs. The solvent was removed from the reaction mixture in vacuo and the reaction mixture was added dropwise to the cold diethyl ether. The resulting precipitate (4) was filtered, dried and the Boc group was deprotected (acidolytic removal) to yield the desired dipeptide ester of acyclovir Val-Val-ACV (5).

Source